157 research outputs found

    (un)Doing standards in education with actor-network theory

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    Recent critiques have drawn important attention to the depoliticized consensus and empty promises embedded in network discourses of educational policy. While acceding this critique, this discussion argues that some forms of network analysis – specifically those adopting actor-network theory (ANT) approaches - actually offer useful theoretical resources for policy studies. Drawing from ANT-inspired studies of policy processes associated with educational standards, the article shows the ambivalences and contradictions as well as the possibilities that can be illuminated by ANT analysis of standards as networks. The discussion outlines the diverse network conceptions, considerations and sensibilities afforded by ANT approaches. Then it shows four phenomena that have been highlighted by ANT studies of educational standards: ordering (and rupturing) practice through ‘immutable mobiles’, local universality, tensions among networks of prescription and networks of negotiation, and different co-existing ontological forms of the same standards. The conclusion suggests starting points, drawing from these ANT-inspired network analyses, for examining policy processes associated with educational standards

    In Vivo Analysis of the Notch Receptor S1 Cleavage

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    A ligand-independent cleavage (S1) in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control

    A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies

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    Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.54

    Uropathogenic Escherichia coli P and Type 1 Fimbriae Act in Synergy in a Living Host to Facilitate Renal Colonization Leading to Nephron Obstruction

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    The progression of a natural bacterial infection is a dynamic process influenced by the physiological characteristics of the target organ. Recent developments in live animal imaging allow for the study of the dynamic microbe-host interplay in real-time as the infection progresses within an organ of a live host. Here we used multiphoton microscopy-based live animal imaging, combined with advanced surgical procedures, to investigate the role of uropathogenic Escherichia coli (UPEC) attachment organelles P and Type 1 fimbriae in renal bacterial infection. A GFP+ expressing variant of UPEC strain CFT073 and genetically well-defined isogenic mutants were microinfused into rat glomerulus or proximal tubules. Within 2 h bacteria colonized along the flat squamous epithelium of the Bowman's capsule despite being exposed to the primary filtrate. When facing the challenge of the filtrate flow in the proximal tubule, the P and Type 1 fimbriae appeared to act in synergy to promote colonization. P fimbriae enhanced early colonization of the tubular epithelium, while Type 1 fimbriae mediated colonization of the center of the tubule via a mechanism believed to involve inter-bacterial binding and biofilm formation. The heterogeneous bacterial community within the tubule subsequently affected renal filtration leading to total obstruction of the nephron within 8 h. Our results reveal the importance of physiological factors such as filtration in determining bacterial colonization patterns, and demonstrate that the spatial resolution of an infectious niche can be as small as the center, or periphery, of a tubule lumen. Furthermore, our data show how secondary physiological injuries such as obstruction contribute to the full pathophysiology of pyelonephritis

    Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

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    Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions

    Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

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    RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

    Phenotypic plasticity of morphological characters in cabbage aphid reared on both radish and cabbage

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    WOS: 000187740600004The effects of both cabbage (Brassica oleracea) and radish (Raphanus sativus) plants on morphological characters in cabbage aphid, Brevicoryne brassicae were examined. The results indicated that host plants had a significant effect on morphological traits of cabbage aphid, all measured traits being larger on radish than on cabbage. Interactions between aphids and their host plants may produce morphological changes in the aphid population, and these changes, due to phenotypic plasticity, may play a crucial role in both host race formation and the sympatric specialisation process

    Phenotypic plasticity in host-plant specialisation in Aphis fabae

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    WOS: 0002344825000051. The study of phenotypic plasticity in host utilisation is crucial for predicting evolutionary patterns of insect-plant interactions. The presence of sufficient variation in plasticity may facilitate host race formation and sympatric speciation. 2. Aphis fabae genotypes showed high levels of phenotypic plasticity in the intrinsic rate of natural increase (r(m)), relative growth rate (RGR), birth weight (BW), adult weight (AW), fecundity (F), and development time (1/d). 3. Thirteen A. fabae genotypes reared both on broad bean and nasturtium exhibited statistically significant genotypic variability in phenotypic plasticity. 4. Some genotypes displayed fitness improvement on novel host plants. 5. Differences in genotypic correlation among fitness components between the two hosts and increased variance on nasturtium indicated different genomic expression on nasturtium. 6. The results indicated that phenotypic plasticity in a novel environment may be a major determinant of the evolutionary trajectory of a parasitic species and might support the idea that speciation starts with phenotypic plasticity
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